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Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis

Uncertainty exists as to whether similar or different mechanisms contribute to the pathogenesis of different subtypes of multiple sclerosis (MS). Detailed analysis of naive T cell homeostasis shows that patients with relapsing-remitting MS (RRMS) and with primary progressive MS (PPMS) have early-ons...

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Autor principal: Haegert, David G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197186/
https://www.ncbi.nlm.nih.gov/pubmed/22096637
http://dx.doi.org/10.1155/2011/461304
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author Haegert, David G.
author_facet Haegert, David G.
author_sort Haegert, David G.
collection PubMed
description Uncertainty exists as to whether similar or different mechanisms contribute to the pathogenesis of different subtypes of multiple sclerosis (MS). Detailed analysis of naive T cell homeostasis shows that patients with relapsing-remitting MS (RRMS) and with primary progressive MS (PPMS) have early-onset thymic involution that causes reduced thymic output. The reduced thymic output leads to secondary peripheral homeostatic alterations in naïve CD4 T-cells, which closely mimic T-cell alterations observed in an experimental animal model of diabetes mellitus. Homeostatic T-cell receptor (TCR) signalling and proliferation of naïve T cells are induced by self-peptides. Consequently, the findings of increased TCR signalling of naïve CD4 T-cells, without increased proliferation, in PPMS, and the increased homeostatic proliferation of naïve CD4 T-cells in RRMS favour the development of autoimmunity. Thus, it seems highly likely that peripheral T-cell alterations secondary to a thymic abnormality contribute to the pathogenesis of both MS subtypes.
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spelling pubmed-31971862011-11-17 Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis Haegert, David G. Mult Scler Int Review Article Uncertainty exists as to whether similar or different mechanisms contribute to the pathogenesis of different subtypes of multiple sclerosis (MS). Detailed analysis of naive T cell homeostasis shows that patients with relapsing-remitting MS (RRMS) and with primary progressive MS (PPMS) have early-onset thymic involution that causes reduced thymic output. The reduced thymic output leads to secondary peripheral homeostatic alterations in naïve CD4 T-cells, which closely mimic T-cell alterations observed in an experimental animal model of diabetes mellitus. Homeostatic T-cell receptor (TCR) signalling and proliferation of naïve T cells are induced by self-peptides. Consequently, the findings of increased TCR signalling of naïve CD4 T-cells, without increased proliferation, in PPMS, and the increased homeostatic proliferation of naïve CD4 T-cells in RRMS favour the development of autoimmunity. Thus, it seems highly likely that peripheral T-cell alterations secondary to a thymic abnormality contribute to the pathogenesis of both MS subtypes. Hindawi Publishing Corporation 2011 2011-09-15 /pmc/articles/PMC3197186/ /pubmed/22096637 http://dx.doi.org/10.1155/2011/461304 Text en Copyright © 2011 David G. Haegert. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Haegert, David G.
Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis
title Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis
title_full Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis
title_fullStr Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis
title_full_unstemmed Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis
title_short Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis
title_sort multiple sclerosis: a disorder of altered t-cell homeostasis
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197186/
https://www.ncbi.nlm.nih.gov/pubmed/22096637
http://dx.doi.org/10.1155/2011/461304
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